Diagnostic Criteria

Suggestive Findings Scenario 1: Abnormal Newborn Screening (NBS) Result NBS for Gaucher disease (GD) is primarily based on quantification of glucocerebrosidase enzyme activity on dried blood spots. Glucocerebrosidase enzyme activity values below the cutoff reported by the screening laboratory are considered positive, and additional testing is required to establish the diagnosis . Scenario 2: Symptomatic Individual GD encompasses a continuum of clinical findings from a perinatal-lethal disorder to type 1 GD with adult onset. GD should be suspected in individuals (by age) with the following combination of central nervous system, bony, hematologic, and other clinical and family history findings . Table 1. Gaucher Disease: Clinical Phenotypes

Source: GeneReviews — "Gaucher Disease"

Differential Diagnosis

Lysosomal Storage Disorders

Findings in Gaucher disease (GD) may overlap with some lysosomal storage diseases ; however, the distinctive clinical features associated with these lysosomal storage disorders, biochemical testing, and an understanding of their natural history should help distinguish between them.

Table 3.

Genes of Interest in the Differential Diagnosis of Gaucher Disease

Gene | Disorder | Key Feature(s) of Disorder Overlapping w/GD | Comment/ Distinguishing Features

Lysosomal storage disorders1

Source: GeneReviews — "Gaucher Disease"

Management Guidelines

Clinical management guidelines for Gaucher disease (GD) have been published . Management by a multidisciplinary team with expertise in treating GD is available at Comprehensive Treatment Centers (see National Gaucher Foundation).

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with GD, the evaluations summarized in or (if not performed as part of the evaluation that led to the diagnosis) are recommended. Recommended evaluations following initial diagnosis can vary based on age at diagnosis, mode of ascertainment (e.g., asymptomatic vs symptomatic individual), and presence or absence of primary neurologic involvement. Baseline (pre-treatment) assessments may be useful in selecting treatment modality and regimen (e.g., enzyme dose, frequency of infusion).

Table 4a.

Gaucher Disease: Recommended Evaluations Following Initial Diagnosis in Adults or Those with Type 1 Gaucher Disease

System/Concern | Evaluation | Comment

General

| Referral to GD treatment center |

Musculoskeletal

| Assess for clinical manifestations of bone disease. |

Radiographs, incl:

• AP femora lateral spine

• Any symptomatic extremities (w/pain, swelling, or warmth to touch)

Clinical Guidance

Nonsteroidal anti-inflammatory drugs should be avoided in individuals with moderate-to-severe thrombocytopenia. The use of anticoagulants in individuals with severe thrombocytopenia and/or coagulopathy should be discussed with a hematologist to avoid the possibility of excessive bleeding.

Source: GeneReviews — "Gaucher Disease"

Therapies Under Investigation

Substrate reduction therapy. Venglustat, an investigational, brain-penetrant glucosylceramide synthase inhibitor, has been administered to adults with type 3 GD receiving imiglucerase. In an early phase clinical trial, addition of once-daily venglustat showed acceptable safety and tolerability and preliminary evidence of clinical stability but inconsistent changes in selected biomarkers . These findings need to be validated and confirmed in future research. Chaperone-mediated enzyme enhancement therapy. Pharmacologic chaperones (PCs), competitive reversible active site inhibitors, serve as a folding template for the defective enzyme during its transit to the endoplasmic reticulum. Such agents may restore enzyme activity within the lysosome and clear stored substrate.

Source: GeneReviews — "Gaucher Disease"

Surveillance Guidelines

Physicians who are the US regional coordinators for the International Collaborative Gaucher Group Registry (ICGG) and other groups have published recommendations for comprehensive serial monitoring of the severity and rate of disease progression [, , , ]. A European working group has also published a consensus document relating to management goals for individuals with type 1 GD . To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended.

Table 6.

Gaucher Disease: Recommended Surveillance

System/Concern | Evaluation | Frequency

General

| Clinical assessment of disease progression using disease severity scoring system (DS3)1 | At least every 12 mos

Clinical disease markers:2

• Lyso-Gb1

• Plasma activity of chitotriosidase (a macrophage-derived chitin-fragmenting hydrolase)

• Plasma PARC/CCL18

Note: Lyso-Gb1 is preferred, if available, obviating the need to monitor w/non-specific biomarker. | At least every 6-12 mos

Musculoskeletal

| Assess for joint pain, range of movement, bone pain

Radiograph of femur (AP view), spine (lateral view), any symptomatic sites | For emergent complaints, or just before treatment modality or dose change

Coronal T1- T2-weighted MRI of hips to distal femur

• T1-weighted MRI to monitor bone marrow infiltration

• T2-weighted MRI to detect bone infarcts, osteonecrosis, osteomyelitis

DXA scan to identify osteoporosis | • In those w/suspected osteoporosis

Source: GeneReviews — "Gaucher Disease"